Autoimmune diseases are the result of a patient's immune system attacking their own cells and tissues. This can result in a wide variety of diseases, including multiple sclerosis, myasthenia gravis, rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, psoriasis, scleroderma, idiopathic thrombocytopenia purpura, and Sjogen's disease. For the most part, the etiology of autoimmune diseases is poorly understood, and attempts at therapeutic intervention have met with limited success.
Recently, it has been discovered that T lymphocytes exist in subpopulations characterized by different patterns of cytokine secretion (Abbas et al., Nature 383:787-793 (1996)). The Th1 subset of CD4.sup.+ T cells promotes inflammatory cellular immune responses and is biased toward the secretion of IFN-.gamma., TNF-.beta., and IL-2. Th2 cells are biased towards the secretion of IL-4, IL-5, IL-6, IL-10, and IL-13, induce humoral immunity, and inhibit Th1 responses. In certain autoimmune diseases, e.g., in type 1 diabetes, it appears that the Th1 pattern of secretion often becomes predominant but the cellular mechanisms integrating the drive to Th1 or Th2 are poorly understood (Kallmann et al., Diabetes 46:237-243 (1997)). One possibility is that disease onset is associated with an expansion or loss of groups of T cells with particular secretory characteristics.
In the mouse, a bias toward Th2 cells may be promoted by the activation of T cells having the V.alpha.14J.alpha.281 receptor (Bendelac et al., Ann. Rev. Immunol. 15:535-562 (1997); Vicari et al., Immunol. Today 17:71-76 (1996)). Humans have been shown to have a population of T cells expressing a receptor, V.alpha.24J.alpha.Q, with a close sequence homology to V.alpha.14J.alpha.281 (Porcelli et al., J. Exp. Med. 178:1-16 (1993)). Defining the relationship between changes in these cells and the onset of autoimmune diseases may lead to new diagnostic and therapeutic procedures.